RESUMEN
The impact of maternal nutrition on neurodevelopment and neonatal neuroprotection is a research topic with increasing interest. Maternal diet can also have deleterious effects on fetal brain development. Fetal exposure to alcohol is responsible for poor neonatal global development, and may increase brain vulnerability to hypoxic-ischemic encephalopathy, one of the major causes of acute mortality and chronic neurological disability in newborns. Despite frequent prevention campaigns, about 10% of women in the general population drinks alcohol during pregnancy and breastfeeding. This study was inspired by this alarming fact. Its aim was to evaluate the beneficial effects of maternal supplementation with two polyphenols during pregnancy and breastfeeding, on hypoxic-ischemic neonate rat brain damages, sensorimotor and cognitive impairments, in a context of moderate maternal alcoholism. Both stilbenoid polyphenols, trans-resveratrol (RSV - 0.15 mg/kg/day), and its hydroxylated analog, trans-piceatannol (PIC - 0.15 mg/kg/day), were administered in the drinking water, containing or not alcohol (0.5 g/kg/day). In a 7-day post-natal rat model of hypoxia-ischemia (HI), our data showed that moderate maternal alcoholism does not increase brain lesion volumes measured by MRI but leads to higher motor impairments. RSV supplementation could not reverse the deleterious effects of HI coupled with maternal alcoholism. However, PIC supplementation led to a recovery of all sensorimotor and cognitive functions. This neuroprotection was obtained with a dose of PIC corresponding to the consumption of a single passion fruit per day for a pregnant woman.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Polifenoles/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Alcoholismo/tratamiento farmacológico , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Lesiones Encefálicas/patología , Disfunción Cognitiva/tratamiento farmacológico , Femenino , Hipoxia/complicaciones , Hipoxia-Isquemia Encefálica/patología , Isquemia/complicaciones , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Intercambio Materno-Fetal/fisiología , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Polifenoles/metabolismo , Embarazo , Ratas , Ratas Wistar , Resveratrol/uso terapéutico , Estilbenos/uso terapéuticoRESUMEN
Hypoxia-ischemia (HI) remains a major cause of perinatal mortality and chronic disability in newborns worldwide (1-6 for 1000 births) with a high risk of future motor, behavioral and neurological deficits. Keeping newborns under moderate hypothermia is the unique therapeutic approach but is not sufficiently successful as nearly 50% of infants do not respond to it. In a 7-day post-natal rat model of HI, we used pregnant and breastfeeding female nutritional supplementation with piceatannol (PIC), a polyphenol naturally found in berries, grapes and passion fruit, as a neuroprotective strategy. Maternal supplementation led to neuroprotection against neonate brain damage and reversed their sensorimotor deficits as well as cognitive impairments. Neuroprotection of per os maternal supplementation with PIC is a preventive strategy to counteract brain damage in pups induced by HI. This nutritional approach could easily be adopted as a preventive strategy in humans.